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Phase 1b/2 Study of TTI-101 in Combination for Patients With Metastatic Hormone Receptor-Positive and HER2-Negative Breast Cancer | Clinical Trials | Clareo Health

TERMINATEDPHASE1

Phase 1b/2 Study of TTI-101 in Combination for Patients With Metastatic Hormone Receptor-Positive and HER2-Negative Breast Cancer

REVERT- Breast Cancer: Phase 1b/2 Study of the Addition of STAT3 Inhibitor TTI-101 to Reverse Resistance to Palbociclib or Ribociclib Plus Aromatase Inhibitor or Fulvestrant Therapy for Metastatic Hormone Receptor-Positive and HER2-Negative Breast Cancer

NCT05384119•Tvardi Therapeutics, Incorporated

View on ClinicalTrials.gov

Summary

The primary objective of Phase 1b will be to evaluate the safety and tolerability of TTI-101 when added to palbociclib and AI or fulvestrant administered orally to participants with hormone receptor-positive (HR+) human epidermal receptor 2-negative (HER2)- palbociclib-resistant breast cancer, and to determine the recommended Phase 2 dose (RP2D) for TTI-101 when added to palbociclib and AI or fulvestrant. The primary objective of Phase 2 will be to evaluate anti-tumor activity in participants who receive TTI-101 added to palbociclib or ribociclib and AI or fulvestrant.

Eligibility

Age

18 - No limit years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•Participants must meet all the following criteria to be eligible:
•1. Age ≥18 years at the time of informed consent.
•2. Metastatic or locally advanced breast cancer not amenable to curative treatment by surgery or radiotherapy.
•3. For Phase 1b,currently receiving palbociclib and AI or fulvestrant; for Phase 2, currently receiving palbociclib or ribociclib and AI or fulvistrant therapy in the metastatic setting with evidence of progressive disease. In addition:
•* Must have remained on palbociclib or ribociclib and AI or fulvestrant therapy for ≥6 months for advanced breast cancer or metastatic disease prior to evidence of progression that in the opinion of the treating physician warrants continued therapy with palbociclib or ribociclib and AI or fulvestrant.
•* Dosage of palbociclib, ribociclib, AI and fulvestrant must remain unchanged from regimen prior to study enrollment specifically palbociclib at a dose of 125, 100, or 75 mg administered orally for 21 days every 28-day cycle or ribociclib at a dose of 200, 400, or 600 mg administered orally for 21 days every 28-day cycle.
•4. All men and premenopausal women must be on medical gonadal suppression therapy with a gonadotropin analog (e.g, goserelin or leuprolide) and have estrogen levels in the postmenopausal range by institutional criteria at baseline.
•5. Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
•6. Has documented confirmation of histological or cytological HR-positive, HER2-negative breast cancer per local laboratory testing.
•7. Up to 2 prior lines of systemic treatment (most recent line of therapy must be palbociclib and AI or fulvestrant for Phase 1b and palbociclib or ribociclib and AI or fulvestrant for Phase 2) in the locally advanced or metastatic setting is allowed; the participant must have shown evidence of progressive disease on palbociclib and AI or fulvestrant for Phase 1b and palbociclib or ribociclib and AI or fulvestrant for Phase 2 in the locally advanced or metastatic setting prior to enrollment.
+3 more criteria

Exclusion Criteria

•1. Has received more than 2 lines of prior systemic therapy for locally advanced/metastatic breast cancer.
•2. Had prior exposure to any signal transducer and activator of transcription 3 (STAT3) inhibitor.
•3. Had radiotherapy within 3 weeks prior to Cycle 1 Day 1 (cycle is 28 days). Participants must have recovered from radiotherapy toxicities prior to starting study treatment and recovered to Grade 1 or better from related side effects of such therapy (with the exception of alopecia).
•4. Has HER2 overexpression by local laboratory testing (immunohistochemical \[IHC\] 3+ or in situ hybridization positive).
•5. Has known loss of retinoblastoma tumor suppressor gene (Rb) (testing not mandatory).
•6. Has had disease progression on more than two cyclin-dependent kinase (CDK)4/6 inhibitors. Adjuvant abemaciclib is allowed but must have progressed on palbociclib or ribociclib.
•7. Concurrently using other anticancer therapy. Participants must continue palbociclib and AI or fulvestrant for Phase 1b and palbociclib or ribociclib and AI or fulvestrant for Phase 2.

Locations (6)

Holy Cross Health Fort Lauderdale - Holy Cross Hospital

Fort Lauderdale, Florida, United States

Washington University School of Medicine Siteman Cancer Center

St Louis, Missouri, United States

Vanderbilt - Ingram Cancer Center

Nashville, Tennessee, United States

Texas Oncology - Dallas Fort Worth (DFW) - Baylor Charles A. Sammons Cancer Center

Dallas, Texas, United States

Harold C. Simmons Comprehensive Cancer Center

Dallas, Texas, United States

University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Key Dates

Start Date

January 9, 2023

Primary Completion Date

April 25, 2024

Completion Date

April 25, 2024

Last Updated

February 21, 2025

Enrollment

ACTUAL participants

Conditions

Breast Cancer

Interventions

TTI-101

DRUG

Palbociclib

DRUG

Aromatase inhibitor (AI)

DRUG

fulvestrant

DRUG

ribociclib

DRUG

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Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: February 21, 2025Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

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Phase 1b/2 Study of TTI-101 in Combination for Patients With Metastatic Hormone Receptor-Positive and HER2-Negative Breast Cancer

Inclusion Criteria

Exclusion Criteria

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